PROCEDIMIENTO PARA LA OBTENCION DE BENZOLSULFONILUREAS

摘要

Novel compounds of the formula and their physiologically tolerable salts, in which X is Cl or Br, A is a C1- 3 alkylene radical and R is a C5- 8 cycloalkyl radical,a cyclohexyl radical substituted by a C1- 3 alkyl or a cyclohexylalkyl radical in which the alkylene chain has 1 or 2 carbon atoms are made by (a) reacting the appropriate benzenesulphonyl iso cyanate benzenesulphonyl carbamic or thio carbamic ester, benzenesulphonyl-carbamic ha lide or benzenesulphonyl urea with an amine RNH2 or a salt thereof; (b) reacting the appropriate benzenesulphonamide or its salt with an R-substituted isocyanate, carbamic or thiocarbamic ester, carbamic halide or urea; (c) hydrolysing the corresponding benzene-sulphonyl-isourea or isothiourea ether or para banic acid; or (d) replacing the sulphur atom by oxygen in a corresponding benzensulphonyl thiourea by means of a heavy metal oxide or an oxidizing agent, and if required, reacting the products with a physiologically tolerated base. In place of the benzenesulphonyl isocyanates in the above process, there may be used compounds which form benzenesulphonyl isocyanates in the course of the reaction. Similarly, the isocyanates of the formula RNCO may be replaced by com pounds which form isocyanates during the reaction. Methyl N - (4 - o - chloroethylbenzenesul phonyl) - carbamate, 4 - o - chloroethylbenzene sulphonyl urea, 4 - o - chloroethyl - benzenesul-phonamide, 1 - cyclohexylparabanic acid, 1 - (4 - o - chloroethylbenzenesulphonyl) - 3 - cyclo hexyl - parabanic acid, 4 - o - chloropropyl benzenesulphonamide, 4 - o - bromoethylben zenesulphonylurea, N - [4 - o - chloroethylben zenesulphonyl] - N1 - cyclohexyl - thiourea, 4 - o -chloroethylbenzenesulphonyl chloride and 4 - o - chloropropylbenzenesulphonyl chloride are pre pared as intermediates. Pharmaceutical preparations having hypo glycaemic activity comprise the above sulphonyl ureas of the invention or their salts, especially the alkali-metal and alkaline earth metal salts, in admixture or conjunction with a carrier preferably in a form adapted to oral administra tion such as tablets.